Article pubs.acs.org/JAFC
Soy Leaf Extract Containing Kaempferol Glycosides and Pheophorbides Improves Glucose Homeostasis by Enhancing Pancreatic β‑Cell Function and Suppressing Hepatic Lipid Accumulation in db/db Mice Hua Li,†,§ Hyeon-Seon Ji,†,‡ Ji-Hyun Kang,† Dong-Ha Shin,# Ho-Yong Park,†,# Myung-Sook Choi,Δ Chul-Ho Lee,⊗ In-Kyung Lee,⊥ Bong-Sik Yun,⊥ and Tae-Sook Jeong*,†,§ †
Industrial Bio-materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea § Department of Biomolecular Science, Korea University of Science and Technology, KRIBB, Daejeon 305-806, Republic of Korea ‡ College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea # Insect Biotech Company Ltd., Daejeon 305-811, Republic of Korea Δ Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 702-701, Republic of Korea ⊗ Laboratory Animal Resource Center, KRIBB, Daejeon 305-806, Republic of Korea ⊥ Division of Biotechnology, Chonbuk National University, Iksan 570-752, Republic of Korea S Supporting Information *
ABSTRACT: This study investigated the molecular mechanisms underlying the antidiabetic effect of an ethanol extract of soy leaves (ESL) in db/db mice. Control groups (db/+ and db/db) were fed a normal diet (ND), whereas the db/db-ESL group was fed ND with 1% ESL for 8 weeks. Dietary ESL improved glucose tolerance and lowered plasma glucose, glycated hemoglobin, HOMA-IR, and triglyceride levels. The pancreatic insulin content of the db/db-ESL group was significantly greater than that of the db/db group. ESL supplementation altered pancreatic IRS1, IRS2, Pdx1, Ngn3, Pax4, Ins1, Ins2, and FoxO1 expression. Furthermore, ESL suppressed lipid accumulation and increased glucokinase activity in the liver. ESL primarily contained kaempferol glycosides and pheophorbides. Kaempferol, an aglycone of kaempferol glycosides, improved β-cell proliferation through IRS2-related FoxO1 signaling, whereas pheophorbide a, a product of chlorophyll breakdown, improved insulin secretion and β-cell proliferation through IRS1-related signaling with protein kinase A in MIN6 cells. ESL effectively regulates glucose homeostasis by enhancing IRS-mediated β-cell insulin signaling and suppressing SREBP-1-mediated hepatic lipid accumulation in db/db mice. KEYWORDS: soy (Glycine max) leaf, kaempferol, pheophorbide a, glucose homeostasis, IRS, SREBP-1
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INTRODUCTION The pathophysiology of type 2 diabetes mellitus (T2DM) is complex, involving insulin resistance, pancreatic β-cell dysfunction, and visceral adiposity. Pancreatic β-cell dysfunction and insulin resistance play a central role in the pathogenesis of diabetes. The predominant defect in T2DM depends on body mass index (BMI). T2DM in Korean patients differs from that in patients in the West, in that Korean patients have low BMIs (
